Nevin Manimala

Gynecol Endocrinol. 2026 Dec 31;42(1):2618881. doi: 10.1080/09513590.2026.2618881. Epub 2026 Jan 22.

ABSTRACT

BACKGROUND: Astrocytes, once regarded as passive support cells, are recognized as active regulators of synaptic organization and neuronal integration. Through extension or retraction of their processes, astrocytes influence synapse formation and elimination. Astrocytes express estrogen receptors, and animal studies have shown that estradiol modifies astrocytic morphology in relation to synaptic density.

OBJECTIVE: To examine the effects of estradiol and two clinically available selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene on astrocyte processes in human brain tissue.

METHODS: Human temporal lobe cortical slices were incubated for 60 min with estradiol (10 nM), tamoxifen (1.0 µM), or raloxifene (1.0 µM), and the results were compared with untreated control slices. Astrocytes were visualized by immunostaining for the glial cytoskeletal marker glial fibrillary acidic protein (GFAP). Light microscopy image analysis was used to quantify astrocytic process thickness and branching, using Neurolucida® software.

RESULTS: Control slices exhibited astrocytic branch extension and thinning during the incubation period. Similar morphological changes were observed in the tamoxifen-treated slices. In contrast, raloxifene treatment was associated with a significant reduction in astrocyte branching and thinning compared with controls (p = 0.01 for primary processes). Estradiol treatment resulted in intermediate reductions in astroglial process measures that did not reach statistical significance.

CONCLUSIONS: Estradiol, tamoxifen, and raloxifene – widely used hormonal agents – were associated with distinct effects on astrocyte morphology in human cortical tissue. These findings support a role for estrogen receptor modulation in astroglial structural regulation and suggest a potential cellular mechanism contributing to central nervous system symptoms reported in clinical settings.

PMID:41568550 | DOI:10.1080/09513590.2026.2618881

Haematologica. 2026 Jan 22. doi: 10.3324/haematol.2025.288956. Online ahead of print.

ABSTRACT

Red blood cell (RBC) transfusions for anemia associated with lower-risk myelodysplastic syndromes/neoplasms (LR-MDS) often contribute to reduced quality of life (QOL). Thus, reduction in RBC transfusion dependency (TD) is a primary therapeutic goal. Imetelstat is a firstin-class, competitive telomerase inhibitor approved to treat certain adult patients with LR-MDS with RBC-TD anemia who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents. In the phase III IMerge study (NCT02598661), treatment with imetelstat resulted in clinically meaningful, statistically significant increases in the primary endpoint of ≥8-week RBC transfusion independence (TI) versus placebo. Because patients with LR-MDS experience detrimental effects on numerous facets of QOL (physical, emotional, social, and functional), these exploratory analyses assessed patient-reported outcomes using the Functional Assessment of Chronic Illness Therapy-Fatigue, Quality of Life in Myelodysplasia Scale, and Functional Assessment of Cancer Therapy-Anemia questionnaires as part of the phase III IMerge study. Nominal P values were reported. Fewer imetelstat-treated patients experienced deterioration in fatigue and more imetelstat-treated patients experienced sustained improvement in fatigue and QOL versus placebo. In the imetelstat group, 8-week, 24-week, and 1-year RBC-TI responders had sustained improvements in predefined significance thresholds versus nonresponders for fatigue (70%, 73%, and 88%, respectively, vs. 37%, 41%, and 44%, respectively; P.

PMID:41568521 | DOI:10.3324/haematol.2025.288956

Curr Drug Targets. 2026 Jan 9. doi: 10.2174/0113894501406097251015114440. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to investigate the expression of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) tissues and its association with the frequency of legume food intake.

METHODS: Clinical data from 93 NSCLC patients at Jiujiang University-affiliated Hospital (2018-2023) were collected. Postoperative recurrence status and legume intake were obtained via telephone follow-up. Fourteen patients with recurrence or metastasis were assigned to the first progression (FP) group. Propensity score matching (1:3) was used to select 42 non-progression (NP) matched patients, totaling 56 for analysis. Patients were divided into low- and high-legume intake groups. EGFR expression was assessed by immunohistochemistry and statistical analysis.

RESULTS: EGFR positivity was higher in the FP group (78.6%, 11/14) than in the NP group (47.6%, 20/42) (P < 0.05). The NP group had a greater proportion of patients with high-frequency legume consumption compared to the FP group (71.4% vs. 35.7%, P < 0.05). Furthermore, patients with high-frequency legume intake (42.9%, 15/35) showed significantly lower EGFR positivity than those in the low-frequency intake group (76.2%, 16/21) (P < 0.05). These results indicate that higher legume intake correlates with both reduced EGFR expression and a decreased postoperative recurrence risk.

DISCUSSION: These findings suggest that higher legume intake is associated with reduced EGFR expression and better postoperative outcomes in NSCLC patients. Legume consumption may modulate disease progression through EGFR regulation.

CONCLUSION: High legume intake correlates with improved prognosis and lower EGFR expression in NSCLC. Further large-scale prospective studies are needed to validate these associations and explore their clinical implications.

PMID:41568509 | DOI:10.2174/0113894501406097251015114440

Curr Top Med Chem. 2026 Jan 9. doi: 10.2174/0115680266377273251010093254. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study was to synthesize and characterize the Formononetin- Celecoxib Conjugate, evaluate its efficacy both in vitro and in vivo, and ascertain its potential as a medicinal agent for osteoarthritis (OA).

METHODS: Phytoconstituents from Glycine max and FDA-approved drugs were meticulously curated and subjected to computational analyses for target identification and molecular docking. The Formononetin-Celecoxib Conjugate was subsequently synthesized and characterized using spectroscopic techniques. In vitro assessments included MTT viability assays and ELISA analyses. In vivo efficacy was evaluated using an MIA-induced OA mouse model.

RESULTS: Molecular Formononetin-Celecoxib Conjugate has high binding affinity towards MMP-9. In vitro, the conjugate was non-toxic and significantly reduced MMP-9 expression. In vivo, it attenuated paw volume (p < 0.05) and prevented body weight loss in OA-induced mice, especially at 200 mg/kg. Statistical analysis (Mean ± SD; two-way ANOVA with Tukey’s test) confirmed significant therapeutic benefits.

DISCUSSION: The study validates the conjugate’s anti-inflammatory and disease-modifying potential through both computational and experimental approaches. Its effects on MMP-9 inhibition suggest translational relevance for human OA. However, small sample size and lack of blinding remain limitations requiring further investigation.

CONCLUSION: Our study demonstrates the promising potential of the Formononetin-Celecoxib Conjugate as a novel therapeutic intervention for OA. By integrating computational predictions with experimental validations, this approach represents a step toward precision medicine in managing OA.

PMID:41568487 | DOI:10.2174/0115680266377273251010093254

Arterioscler Thromb Vasc Biol. 2026 Jan 22. doi: 10.1161/ATVBAHA.125.324017. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity predisposes individuals to multiple pathologies, including metabolic dysfunction-associated steatotic liver disease and diabetes. Although it is known that accumulation of proinflammatory macrophages within adipose tissues drives adiposity and provokes obesity-linked sequelae, the molecular mechanisms that provoke macrophage dysfunction in obesity remain elusive. Macrophages express high levels of uPA (urokinase plasminogen activator), and uPA has been implicated in leukocyte migration.

METHODS: Human adipose tissues from patients receiving bariatric surgery were collected and analyzed for uPA protein levels. To determine the impact of uPA in adipose tissue and subsequent high-fat diet (HFD)-induced weight gain and metabolic diseases, a novel mouse model with a conditional knockout of uPA (Plau^fl/fl) was generated. Plau^WT/WT, Plau^KO/KO (global uPA deficiency), and Plau^fl/fl/LysM Cre+ (conditional uPA deficiency in macrophages) mice were fed low-fat diet or HFD for up to 20 weeks.

RESULTS: Protein levels of visceral adipose tissue uPA positively correlated with body mass index in patients with obesity, and uPA levels decreased in adipose tissue 2 years after bariatric surgery. The expression and activity of uPA also increased in the adipose tissue of HFD-fed control mice. Plau^KO/KO mice displayed reduced weight gain and metabolic sequelae through 14 weeks on a HFD compared with Plau^WT/WT mice, but not with prolonged HFD feeding. Interestingly, Plau^fl/fl/LysM Cre+ mice developed HFD-induced metabolic pathologies equivalently to Plau^WT/WT mice.

CONCLUSIONS: Our findings suggest that global uPA deletion, but not selective deletion of uPA in LysM+ myeloid cells, attenuates the development of early-stage HFD-driven obesity and pathologies consistent with metabolic syndrome.

PMID:41568458 | DOI:10.1161/ATVBAHA.125.324017

Circ Cardiovasc Imaging. 2026 Jan 22:e018677. doi: 10.1161/CIRCIMAGING.125.018677. Online ahead of print.

ABSTRACT

BACKGROUND: Computed tomography based planimetric assessment of the anatomic aortic valve area (aAVA^CTA) in aortic stenosis is routinely performed. Unlike transthoracic echocardiography-based effective AVA by transthoracic echocardiography, it lacks clearly defined severity cutoff values, limiting clinical utility.

METHODS: In this retrospective single-center analysis with computed tomography angiography data from 2013 to 2025, cutoffs were determined from 1294 transthoracic echocardiography-based conclusive severe or nonsevere patients by congruence of maximum velocity, mean pressure gradient, and effective AVA by transthoracic echocardiography. In separate receiver operator curves analyses for tricuspid and bicuspid valves, the severe stenosis likely cutoff was defined by Youden index and the unlikely cutoff by a negative likelihood ratio <0.1. Cutoffs were internally validated in 480 patients, compared with the Agatston score by net reclassification index, and tested in 190 separate normal flow-low gradient-aortic stenosis cases.

RESULTS: Correlation between aAVA^CTA and effective AVA by transthoracic echocardiography was moderate and strong in tricuspid and bicuspid valves, respectively (Pearson r 0.67 and 0.78; P<0.001). Severe stenosis was likely in tricuspid valves at aAVA^CTA ≤0.95 cm² (sensitivity 87%, specificity 78.9%) and unlikely at ≥1.10 cm² (negative likelihood ratio, 0.092). In bicuspid valves severe stenosis was likely at aAVA^CTA ≤1.08 cm² (sensitivity 88.3%, specificity 77.3%) and unlikely at ≥1.20cm² (negative likelihood ratio, 0.091). Validation showed comparable results. Net reclassification index compared with the Agatston score was 0.16 for likely and 0.17 for unlikely cutoffs (P<0.001). Cutoffs were applied to 190 suspected severe low-gradient cases. Adding aAVA^CTA as an additional severity marker led to reclassification to nonsevere in 5.8% of cases.

CONCLUSIONS: Direct planimetry of AVA is feasible and shows utility in low gradient-aortic stenosis. However, as the hemodynamic effect is impacted by valve shape, cutoff values should differentiate between tricuspid and bicuspid valves.

PMID:41568440 | DOI:10.1161/CIRCIMAGING.125.018677

J Interprof Care. 2026 Jan 22:1-13. doi: 10.1080/13561820.2025.2609088. Online ahead of print.

ABSTRACT

Validating an interprofessional education and collaborative practice (IPECP) curriculum prior to implementation is uncommon. A sound empirical investigation involving external and internal participants considered four criteria: relevance, consistency, practicality, and effectiveness, as part of an educational design research process to assess whether the proposed curriculum content was valid for the South African healthcare higher education context. Participants provided quantitative input on the four criteria on a visual analog scale (0-100) and qualitative comments to suggest improvements to the proposed curriculum. Descriptive statistics and deductive thematic analysis were used for data analysis. The participants lauded the proposed curriculum. Relevance generated strong agreement and consensus (m = 99, IQR = 6.75), with a lower, but still adequate, rating and consensus for practicality (m = 85.5, IQR = 25.75). The consistency and effectiveness, rated across years of study and streams, indicated in ratings and consensus with an increase across years of study from the first to the last year. Of the streams, the proposed Research and Ethics stream appeared to be the most problematic with moderate consensus (m = 90, IQR = 19.75). Curriculum validation before implementation illuminated concerns requiring refinement and strengthening responsive strategies to ensure a tailored implementation of the proposed curriculum.

PMID:41568431 | DOI:10.1080/13561820.2025.2609088

Pharmacotherapy. 2026 Jan;46(1):e70102. doi: 10.1002/phar.70102.

ABSTRACT

BACKGROUND: Although donor-derived cell-free DNA (dd-cfDNA) serves as a monitoring tool for rejection, few studies have examined its utility in guiding immunosuppression management. Here, we present the largest kidney transplant population in which immunosuppression minimization and subsequent surveillance were guided by dd-cfDNA.

METHODS: This retrospective case series evaluated our immunosuppression minimization practice to tacrolimus and prednisone in kidney transplant recipients (KTR) from November 20, 2020, to September 26, 2024. Baseline dd-cfDNA ≤ 0.5% was required before minimization. Immune tolerance was defined by the absence of any immune event after minimization: absolute dd-cfDNA > 0.5%, relative change value (RCV) > 60% from baseline, biopsy-proven acute rejection (BPAR), or de novo donor-specific antibody (DSA). All other KTR were labeled intolerant. The primary endpoint was the rate of immune tolerance.

RESULTS: Immunosuppression was modified to tacrolimus and prednisone in 38 KTR at a median of 223 days post-transplant. Most KTR were older adults at low immunological risk: mean of 69 years and all had a calculated panel reactive antibody of 0%. 21 (55.3%) KTR met the primary end point of tolerance. The remaining 17 KTR were labeled intolerant secondary to dd-cfDNA elevations including absolute > 0.5% or RCV > 60% (n = 16 of 17, 94%), de novo DSA (n = 2 of 17, 11.8%), and/or BPAR (n = 4 of 17, 23.5%). Although not statistically significant, intolerant KTR were numerically more likely to have 5-6 HLA mismatches (82.5% vs. 52.4%, p = 0.31), less likely to have thymoglobulin induction (29.4% vs. 42.9%, p = 0.39), and were minimized earlier after transplant (196 vs. 256 days, p = 0.08) compared with tolerant KTR, respectively. Intervention after dd-cfDNA elevations included immunosuppression increase (50%), additional dd-cfDNA monitoring (81.3%), DSA testing (50%), and allograft biopsy (18.7%).

CONCLUSION: Approximately 50% of low immunological risk KTR with a baseline dd-cfDNA < 0.5% tolerated immunosuppression minimization to tacrolimus and prednisone without concerning dd-cfDNA elevations, BPAR, or DSA. Our study highlights the role of dd-cfDNA as part of the armamentarium for identifying minimization candidates and performing subsequent surveillance.

PMID:41568414 | DOI:10.1002/phar.70102

J Neurosurg Anesthesiol. 2026 Jan 22. doi: 10.1097/ANA.0000000000001086. Online ahead of print.

ABSTRACT

BACKGROUND: The association between intraoperative hypotension and delirium in patients with brain tumors remains unclear. We thus evaluated the association between intraoperative hypotension and postoperative delirium in patients recovering from neurological surgery.

METHODS: This was a secondary analysis of 3 prospective studies. Patients aged greater than 18 years who were scheduled for elective craniotomy for resection of glioma or frontotemporal lobe tumor were enrolled. Intraoperative hypotension was quantified through 3 metrics: mean arterial pressure area under the curve, time-weighted mean arterial pressure, and cumulative duration of hypotension. Our primary outcome was the association between hypotension and postoperative delirium.

RESULTS: The study comprised 738 patients (median age 56 y; 50% male) undergoing craniotomy for brain tumor resection. Postoperative delirium occurred in 29.0% (95% CI: 25.7%-32.3%) of patients. No statistically significant associations between intraoperative hypotension (absolute mean arterial pressure 60 to 75 mm Hg, relative reductions 10% to 40% from baseline) and postoperative delirium. However, the presence of preoperative tumor midline shift was an independent risk factor for postoperative delirium (adjusted odds ratio: 1.56, 95% CI: 1.09-2.22, P=0.014), and interacted with time-weighted average mean arterial pressure at relative reductions 10% based on the subgroup analysis.

CONCLUSIONS: In adult patients undergoing elective craniotomy for tumor resection, no significant association is found between intraoperative hypotension and postoperative delirium.

PMID:41568401 | DOI:10.1097/ANA.0000000000001086

Stat Med. 2026 Jan;45(1-2):e70369. doi: 10.1002/sim.70369.

ABSTRACT

The objective of this study is to perform variable selection and parameter estimation for analyzing partly interval-censored data based on a proportional hazards model that incorporates spatial effects. To broaden the model’s applicability across diverse scenarios, we consider two types of spatial structures: adjacency and distance information. Leveraging the differentiable properties of the $l_1$ -ball prior developed through projection-based methods, we have devised an efficient Bayesian algorithm by introducing latent variables and applying stochastic gradient Langevin dynamics principles. This algorithm can rapidly deliver results without resorting to complex sampling steps. Through simulations encompassing various scenarios, we have validated the performance of this method in both variable selection and parameter estimation. In our real data application, the proposed approach selects important variables associated with the emergence time of permanent teeth. Additionally, it identifies the spatial structure that best fits these data characteristics. This selection and identification are based on two Bayesian model selection criteria: the log pseudo-marginal likelihood and the deviance information criterion.

PMID:41568399 | DOI:10.1002/sim.70369